The purpose of the proposed supplement is to request funds to expand the multi-system assessment of biomarkers in a currently funded PO1 entitled "Integrative Pathways to Health and Illness." The study, known as MIDUS (Midlife in the U.S.), involves a longitudinal sample of nearly 7,000 Americans, including a large sample of twins, aged 34 to 84. Comprehensive psychosocial, sociodemographic and health data were obtained approximately 10 years ago. We are now repeating those assessments, plus adding diverse biomarkers. The funded PO1 includes five interrelated projects, one of which (Project 4) involves biology where we are assessing neuroendocrine, immune, cardiovascular factors on approximately 1,550 MIDUS respondents at one of three sites around the U.S. To this agenda, we seek to add new measures that will expand our assessment of allostatic load, which is differentiated into multiple categories of primary mediators and secondary outcomes. For primary mediators, we seek to add new measures of inflammation (C-reactive protein (CRP), intercellular adhesion molecules (ICAM), E-setectin) as well as antioxidants (tocopherol and carotenoids) that may serve as buffers against oxidative stress. Regarding secondary outcomes, we seek to add a new measure of coagulation (fibrinogen) as well as multiple measures of bone health (bone mineral density; bone turnover: bone specific alkaline phosphates (BSAP), n-teleopeptide Type 1 collagen (NTx), aminoterminal propeptide type 1 collagen (PINP), and a marker of muscle turnover and impaired kidney function (creatinine clearance). The proposed additions involve minimal increments to respondent burden, but will afford major gains in the scope of testable hypotheses regarding the biological signature of cross time accumulation of adversity of advantage across multiple life domains as well as hypotheses about interrelationships among the biomarkers themselves. Recursive partitioning is elaborated as a methodology for testing the integrative hypotheses detailed in the proposal. [unreadable] [unreadable]